Adiposopathy: Treating pathogenic adipose tissue to reduce cardiovascular disease risk

Abstract

Excessive adipose tissue is potentially pathogenic due to its mass effects and through adverse metabolic/immune responses, which may lead to cardiovascular disease risk factors (eg, type 2 diabetes mellitus, hypertension, dyslipidemia, and possibly atherosclerosis itself). Positive caloric balance in genetically/environmentally susceptible patients may result in adipocyte hypertrophy, visceral adipose tissue accumulation, and ectopic fat deposition, all causally associated with metabolic disease, and all anatomic manifestations of "adiposopathy" (a term used to describe adipose tissue pathology). Weight loss through improved nutrition, increased physical activity, and weight loss agents (ie, orlistat and sibutramine) improves adiposopathy and improves many metabolic diseases whose prevalence are directly associated with an increase in body fat and sedentary lifestyle. Cannabinoid receptor antagonists improve adiposopathy through weight reduction and favorable metabolic effects upon multiple body organs (including adipocytes). Peroxisome proliferator-activated receptor-gamma agonists may improve adiposopathy through recruitment of functional fat cells and apoptosis of dysfunctional fat cells.

Adiposopathy

“…From a cardiovascular treatment standpoint, a paradoxical clinical scenario is adding fat as a means to treat diseases often associated with too much fat (33). PPAR-gamma agonists increase the recruitment, proliferation, and differentiation of functional fat cells in SAT relative to VAT (2,54,70). Increased adipogenesis helps account for how PPAR-gamma agents increase body fat, improve adipocyte function, lower glucose levels in patients with T2DM, reduce heptatic steatosis (55,137), and helps explain how some PPAR gamma agents improve lipid parameters (138) and potentially reduce CVD risk (139).…”

Local adipose tissue renin-angiotensin system

“…Adipose tissue located in the upper, or central, part of the body generally makes up about 20% of total fat. Although subcutaneous adipose is by far the largest adipose depot within the human body, visceral adipose boasts higher metabolic activity, with direct access to the liver via the portal vein [1]. Similarly, human visceral adipose tissue exhibits significantly elevated angiotensinogen mRNA compared with subcutaneous adipose tissue [32].…”

“…In the past, adipocytes were recognized as an inert energy source; however, adipocytes are now known to synthesize and secrete proinflammatory factors such as cytokines, acute-phase response proteins, chemotactic/chemoattractants, eicosanoids, prostaglandins, and potentially anti-inflammatory effectors (eg, adiponectin, interleukin [IL]-6, and IL-10) [1]. Collectively, these adipocyte-derived factors have been termed adipokines They have increased steadily over the years; more than 50 different adipokines are now known to be secreted from adipocytes.…”

The metabolic syndrome: common origins of a multifactorial disorder

“…However, more specifically, one of the most important causal components of MetS is the accumulation of “ectopic” fat. This often results in a pathophysiological condition that has recently been termed “adiposopathy”, and is defined as pathogenic adipose tissue that is promoted by a positive energy balance and sedentary lifestyle in genetically and environmentally susceptible patients 22 23 24. Adiposopathy is thought to be clinically manifest through a combination of adipocyte hypertrophy, adipose tissue growth, ectopic fat distribution and, especially, visceral adipose tissue accumulation, all of which may cause adverse immune and metabolic disturbance24 and may contribute to the development of MetS.…”